Effects of GJB2 genotypes on the audiological phenotype: Variability is present for all genotypes

Recent studies have revealed a genotype–phenotype correlation for mutations in the GJB2 gene. Since ethnic difference may have an effect for the degree of hearing loss due to background genes, we aimed to search for confirmation of previously suggested genotype–phenotype correlation in GJB2 deafness in the Turkish population. Pure tone audiograms of 63 unrelated probands with GJB2-associated hearing loss having 15 different mutations were obtained and evaluated for correlation between the degree of hearing loss and genotypes. Three GJB2 genotypes identified in more than one family were homozygous c.35delG (44 probands), homozygous p.E120del (four probands) and c.[35delG] + [IVS1 + 1G > A] (two probands). No statistical difference for the degree of hearing loss was observed when the genotypes were compared individually or grouped according to their effects on the protein. The most likely explanation for this result is the relatively small size of the studied population. Degree of hearing loss was variable in c.35delG and p.E120del homozygotes. Intra-familial phenotypic variability was present for some genotypes. The detailed audiological data for homozygous p.E120del and c.[35delG] + [328delG] genotypes are reported for the first time in this study. Previously reported genotype–phenotype correlations for the GJB2 deafness should be cautiously interpreted during the clinical counseling since variability in the degree of hearing loss is present for all GJB2 genotypes

SLC26A4 mutations are associated with a specific inner ear malformation

Inner ear anomalies have been reported in approximately 30% of children with early onset deafness. Identification of causative genetic factors in a large proportion of these patients was not successful. Mutations in the SLC26A4 gene have been detected in individuals with enlarged vestibular aqueduct (EVA) or Mondini dysplasia. We aimed to characterize the inner ear anomalies associated with SLC26A4 mutations. The SLC26A4 gene has been screened for mutations in 16 subjects from 14 unrelated Turkish families with a variety of inner ear anomalies ranging from Michel aplasia to incomplete partition-II and EVA. None of the patients was diagnosed to have a recognizable genetic syndrome. Additional four patients with Pendred syndrome from three families were included. Only one patient with EVA was found to have a heterozygous mutation (c.1586delT) in SLC26A4. All patients with Pendred syndrome had homozygous mutations and were noted to have either EVA or EVA associated with incomplete partition-II on the computed tomography of the temporal bone. SLC26A4 mutations are not associated with a large spectrum of inner ear anomalies. They, instead, result in a specific morphological appearance consistent with EVA or incomplete partition-II

Evaluation of the Impact of Cochlear Implantation on Patients’ Working Life: A Cross-Sectional Study

Hearing loss that arises from various causes at different stages of life has a direct impact on individuals’ physical and mental well-being. This paper aimed to evaluate the employment, workplace adaptation, productivity, and professional success of individuals who have hearing loss and whose hearing loss is corrected with a cochlear implant. In this cross-sectional study, data were collected between November 2022 and March 2023 with the participation of individuals with cochlear implants living in several settlements in all regions of Türkiye. A total of 142 participants with severe hearing loss who were corrected with a cochlear implant were included in this study. The survey method was used to collect data for the study. The questionnaire consisted of 32 questions and was distributed to the participants online. In the first part of the questionnaire (questions 1–10), the general characteristics of implant patients were investigated. In the second part (questions 11–32), the positive or negative effects of implantation on the work lives of the participants were evaluated. Almost half of the research group (49.3%, n = 70) consisted of women, and the mean age of the participants was determined to be 35.8 ± 14.8 years. There was no significant difference between gender, educational status, implanted side, working time, working style (physical, desk), and factors affecting work life (p > 0.05). Professional satisfaction and success at work increased significantly more in those with acquired hearing loss (p = 0.010). Post-implantation workplace compliance, success, and productivity were found to be higher in those with acquired hearing loss (p = 0.013). Hearing loss had a significantly less negative impact on work performance in those implanted in childhood than in those implanted in adulthood (p = 0.043). It was observed that hearing loss had a greater negative impact on the work life of married people (p = 0.006). Cochlear implantation greatly enhances workplace satisfaction, increases self-confidence, and has a positive impact on the future of profoundly deaf individuals

Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating

Considerable differences exist for the spectrum of GJB2 mutations in different populations. Screening for the c.35delG mutation in 256 independent probands, 154 multiplex (familial) and 102 simplex (sporadic), coming from different regions of Turkey revealed 37 (14.5%) homozygotes. The allele frequency of c.35delG ranged from 5% to 53% in different cities. Parental consanguinity was noted in 34% of c.35delG homozygotes, yet it was 55% in c.35delG negatives (p=0.034). Further screening for GJB2 mutations in multiplex families demonstrated the presence of c.167delT and L90P mutations as well as a novel complex mutation, c.236_239delTGCAinsAGATCCG, in single alleles, leading to compound heterozygosity with c.35delG. The homozygous E120del mutation was found in another case. The V27I polymorphism was detected in five alleles, one of which was associated with the E114G change. Assortative mating was a significant factor predicting to detect biallelic mutations in the GJB2 gene. These results confirm the overwhelming majority of c.35delG in the Turkish deaf individuals as well as the presence of other changes detected in Caucasian and Asian populations

Vocal Fold Hyperplastic Lesions: an Evaluation of Surgical Outcome with Videolaryngostroboscopy

Background: Vocal fold hyperplastic lesions are premalignant lesions that can be treated effectively by removal of the lesions surgically. Aims: The aim of this study was to discuss the success of surgery in patients with vocal fold hyperplastic lesions in terms of preserving vibratory function by comparing the preoperative and postoperative videolaryngostroboscopy findings. Study Design: The medical charts and videolaryngostroboscopic recordings of patients diagnosed with hyperplastic lesions on the vocal folds were reviewed retrospectively. Methods: Twenty seven patients with unilateral lesions who underwent type1 subepithelial cordectomy were enrolled in the study. The videolaryngostroboscopic recordings were evaluated by three raters who were not the operating surgeon and who were blinded to the histology of patients. To evaluate the videolaryngostroboscopic findings, a form, which is a modification of criteria described by Hirano and Bless, was used. Preoperative and 6th month postoperative videolaryngostroboscopic recordings were compared with each other and with recordings of the control group, which included 50 healthy volunteers. Results: All videolaryngostroboscopic findings, except false cord vibration, were significantly improved after surgery. Conclusion: The principle of vocal fold surgery in patients with benign lesions is to preserve the vibratory tissue. This principle also applies to patients with hyperplastic lesions that are premalignant. The hydrodissection technique may be beneficial for this purpose

In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma

Objectives: To investigate cytokine profile of cholesteatoma and to collect information about important intercellular signaling pathways by establishing two different cell culture models, to block important intercellular signaling pathways in cholesteatoma by applying immune system modifier drugs to develop alternative medical therapy options for cholesteatoma. Methods: To observe the pathogenesis of cholesteatoma and to apply the immunomodulatory drugs, cholesteatoma tissue culture models were constituted with HEKa cells and cholesteatoma keratinocytes, which were obtained from 3 patients who underwent operations for cholesteatoma. Medicines including 5-fluorourasil, imiquimod, cyclosporine, and tacrolimus were applied on both cholesteatoma keratinocytes and HEKa cells. After 48 h of incubation, IL-1, IL-6, IL-8, IL-10, TNF-alpha, and Ki67 levels were measured to determine cell viability rates. Results: In the cholesteatoma control group, IL-6 and TNF-alpha levels were found higher than in the HEKa control group. All repurposed drugs in the study demonstrated anti-inflammatory, anti-proliferative, and cytotoxic effects on cholesteatoma. Imiquimod and tacrolimus in particular are potential treatment prospects for cholesteatoma due to their strong anti-inflammatory and cytotoxic effects. Conclusion: Medical therapy options for cholesteatoma are still missing and surgery is not the ultimate solution. We have focused on intercellular inflammatory processes, which play significant roles in the pathogenesis of cholesteatoma in our paper. Inflammation and proliferation of cholesteatoma decreased after all repurposed drug applications in our study. Anti-inflammatory and anti-proliferative effects of tacrolimus and imiquimod was more significant than other drugs in the study. For this reason, tacrolimus and imiquimod should be examined in depth with in vivo studies in terms of efficacy and safety for medical treatment of cholesteatoma.Eskisehir Osmangazi University BAP FundEskisehir Osmangazi UniversityThis study has been funded by Eskisehir Osmangazi University BAP Fund